The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions.
We have matched a PCR assay which detects disruptions in the E2 reading frame of human papillomavirus type 16, with RNA in situ hybridization patterns and shown that in 15 out of 16 cervical intraepithelial neoplastic (CIN) III lesions and in 19 out of 19 tumours, the E2 gene is disrupted with no detectable E2 transcripts. Varying levels of E6–E7 transcripts are detected in CIN III lesions, with stronger signals in tumours. The cytokeratin profile of most tumours: cytokeratin 10-, 14- and 19-positive and 4-, 13- and 18negative, is also detected in CIN III lesions. The changes in levels of α2, β1 and β4 integrins, CD44 and E-cadherin occur during the evolution of high-grade CIN lesions. Increases in the levels of expression of CD44 and E6-E7 transcripts, coupled with changes in the cellular localization of the Notch protein, define the transition from CIN III lesions to tumours.
BartschD.,
BoyeB.,
BaustC.,
zur HausenH.,
SchwartzE.1992; Retinoic acid-mediated repression of human papillomavirus 18 transcription and different ligand regulation of the retinoic acid receptor gene in non-tumorigenic and tumorigenic HeLa hybrid cells. EMBO Journal 11:2283–2292
CullenA. P.,
ReidR.,
CampionM.,
LorinczA. T.1991; Analysis of the physical state of different human papillomavirus DNAs in intraepithelial and in invasive cervical neoplasm. Journal of Virology 65:606–612
DanielB.,
MukherjeeG.,
SeshadriL.,
VallikadE.,
KrishnaS.1995; Changes in the physical state and expression of human papillomavirus type 16 in the progression of cervical intraepithelial neoplasia lesions analysed by PCR. Journal of General Virology 76:2589–2593
DasB. C.,
SharmaJ. K.,
GopalakrishnaV.,
LuthraU. K.1992; Analysis by polymerase chain reaction of the physical state of human papillomavirus type 16 DNA in cervical preneoplastic and neoplastic lesions. Journal of General Virology 73:2327–2336
Di LucaD.,
PilottiS.,
StefanonB.,
RotolaA.,
MoniniP.,
TognonM.,
De PaloG.,
RilkeF.,
CassaiE.1986; Human papillomavirus type 16 DNA in genital tumours: a pathological and molecular analysis. Journal of General Virology 67:583–589
DongX. P.,
StubenrauchF.,
Beyer-FinklerE.,
PfisterE.1994; Prevalence of deletions of YY1 binding sites in episomal HPV 16 DNA from cervical cancers. International Journal of Cancer 58:803–808
DürstM.,
KleinheinzA.,
HotzM.,
GissmannL.1985; The physical state of human papillomavirus type 16 DNA in benign and malignant genital tumours. Journal of General Virology 66:1515–1522
DürstM.,
GlitzD.,
SchneiderA.,
zur HausenH.1992; HPV 16 gene expression and DNA replication in cervical neoplasia: analysis by in situ hybridisation. Virology 189:132–140
EllisenL. W.,
BirdJ.,
WestD. C.,
SorengA. L.,
ReynoldsT. C.,
SmithS. D.,
SklarJ.1991; TAN-1 the human homolog of the Drosophila Notch gene, is broken by chromosomal translocations in T lymphoblastic neoplasms. Cell 66:649–661
LehnH.,
VillaL. L.,
MarzionaF.,
HilgarthM.,
HillemansH.-G.,
SauerG.1988; Physical state and biological activity of human papillomavirus genomes in precancerous lesions of the female genital tract. Journal of General Virology 69:187–196
Stetler-StevensonW. G.,
AznavoorianS.,
LiottaL. A.1993; Tumour cell interactions with the extracellular matrix during invasion and metastasis. Annual Review of Cell Biology 9:541–573
ZagourasP.,
StifaniS.,
BlaumuellerC. M.,
CarcangiuM. L.,
Artavanis-TsakonasS.1995; Alterations in Notch signalling in neoplastic lesions of the human cervix. Proceedings of the National Academy of Sciences, USA 92:6414–6418
The link between integration and expression of human papillomavirus type 16 genomes and cellular changes in the evolution of cervical intraepithelial neoplastic lesions.